ArticleScientific reports2026
IRF9-dependent transcriptional regulation of SLC40A1 suppresses ferroptosis in dilated cardiomyopathy.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The specific involvement and regulatory mechanisms of programmed cell death (PCD) subtypes in the pathogenesis of dilated cardiomyopathy (DCM) remain poorly characterized. This study aims to systematically investigate PCD network alterations and identify pivotal therapeutic targets in DCM progression. We performed Gene Set Variation Analysis (GSVA) enrichment analysis across two clinical DCM transcriptomic datasets to evaluate the activity of 18 PCD pathways. Following differential and protein-protein interaction (PPI) network analyses, the crucial hub gene was identified. The cardioprotective role of this gene was subsequently validated both in vitro (doxorubicin-induced cardiomyocyte injury) and in vivo (rat DCM model). Functional assessments included EdU incorporation, TUNEL staining, echocardiography, and redox homeostasis evaluations (GPX4, MDA, and GSH levels). Bioinformatic analysis revealed that the enrichment patterns of three PCD pathways were significantly dysregulated in DCM, with the ferroptosis pathway signature demonstrating the most prominent alteration. Integrated analysis identified the iron exporter SLC40A1 as a central hub gene, which was notably upregulated in DCM. Single-cell RNA sequencing further corroborated the pronounced upregulation of SLC40A1 in surviving cardiomyocytes and highlighted its extensive intercellular communication. In vitro and in vivo validation demonstrated that SLC40A1 overexpression significantly promoted cardiomyocyte proliferation, reduced apoptosis, and mitigated pathological cardiac remodeling and systolic dysfunction. Mechanistically, SLC40A1 overexpression exerted its cardioprotective effects by suppressing ferroptosis, evidenced by upregulated GPX4 expression, decreased lipid peroxidation (MDA), and restored intracellular GSH levels. Furthermore, dual-luciferase assays confirmed that the transcription factor IRF9 directly regulates SLC40A1 expression to modulate cellular redox status. Our multi-omics and experimental approach identifies SLC40A1 as a critical endogenous suppressor of ferroptosis in DCM pathogenesis, driven by IRF9-dependent transcriptional regulation. Enhancing the IRF9/SLC40A1 axis provides a novel therapeutic strategy for mitigating ferroptosis-mediated cardiac injury in cardiomyopathy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.